Abstract A combination of cytotoxic chemotherapeutic drugs, such as gemcitabine and cisplatin (GC), is part of the standard of care for advanced bladder cancer. Neoadjuvant GC treatment can induce complete remission (no evidence of viable cancer cells), but less than 40% of patients respond and the regimen is toxic. Thus, there remains an unmet medical need to develop less toxic and more effective chemotherapy options for bladder cancer. We are developing an orally bioavailable drug candidate called PTUPB which has such properties. The compound has anti-inflammatory and anti-angiogenic mechanisms of action as demonstrated in several rodent models of metabolic syndrome and cancer. PTUPB potentiates cisplatin and GC efficacy in a bladder cancer mouse PDX models. We propose to extend this work to include determination of dose-dependent PK and anti-tumor activity and preliminary toxicity assessment for PTUPB as a single agent and in combination with GC therapy in an established patient derived xenograft (PDX) mouse model of bladder cancer. Progression free and overall survival will be assessed along with pharmacokinetic profiling, blood panels and histology assessment of selected tissues.